1. The lipophilicity of the drug affect the oral absorption and distribution. The more lipophilic the drug the easier and thus faster it enters the Central Nervous System, through crossing the blood-brain-barrier. Also the conversion of a prodrug, for example Clorazepate, via acid hydrolysis in the stomach, to an active form. In the case of Clorazepate the active form is desmethyldiazepam which can be absorbed into the blood. Thus this determines the time of onset of effects of this drugs (Katzung, 2018).
2. Redistribution is the fast distribution of highly lipid soluble drugs to the kidneys, brain and heart but are excreted quickly forming a depot in fat and muscles. This drugs can now be released at a slow pace from this depot. The drugs that are redistributed are eliminated slowly and will not be eliminated within 24 hours (Brand, 2021).
3. Benzodiasepine-metabolism consists of 3 steps which cause biotransformation of the drugs through hepatic microsomal enzymes:

Step 1: Dealkylation

This dealkylation of the benzodiazepines forms active metabolites of the drug.

Step 2: Oxidation via cytochrome P450 enzymes

The P450 enzymes, especially the CYP3A4, catalyze alphilic hydroxylation of the benzodiazepines to form active metabolites.

Step 3: Conjugation

Glucuronic acid forms water soluble glucoronides, of the active metabolites, which is excreted in the urine. This glucoronides are inactive metabolites (Brand, 2021).

4. Prazepam, Diazpam and Chlirdiazepoxide and Chlorazepate. Active metabolites formed, form the last mentioned benzodiazepines, has an extended duration of action. Cumulative effects could be caused by multiple doses (Brand, 2021; Katzung, 2018).
5. Temazepam, lormetazepam, lorazepam and oxazepam. This drugs can be useful to give to patient with a decreased cytochrome P450 activity, eg. an elderly patient, patients with liver cirrhosis, if a patient is using P450-enzymes and also neonates of mothers who used benzodiazepines before the neonate’s birth (Brand, 2021).
6. Enzyme induction is the induced expression of an enzyme due to the repeated administration of a specific drug. This induced expression happens by a reduction in the rate of degradation or  increasing the rate of synthesis. The result of induction is an acceleration of substrate metabolism. This usually cause a decrease in the pharmacologic action. Certain old sedative-hypnotic drugs, used long-term, may increase hepatic microsomal drug metabolizing enzyme activity. Examples of this drugs is meprobamate and barbiturates, especially phenobarbital. This drugs then cause induction by increasing hepatic metabolism (Katzung, 2018).

Reference list

Brand, L. 2021. Sedative-hypnotic drugs. Study unit 2 [pdf]. Unpublished lecture notes on eFundi, FKLG312. Potchefstroom: NWU.

Katzung, B.G. 2018. Basic & Clinical Pharmacology. 14th ed. International: Mc Graw Hill Education.